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Efficacy and safety of permissive hypercapnia in preterm infants: A systematic review
Yuri Ozawa1,2, Fuyu Miyake2,3, Tetsuya Isayama2
1Division of Pediatrics, Kyorin University, Tokyo, Japan.
Insights
Permissive hypercapnia did not show significant benefits or harms in preterm infants on mechanical ventilation. Further trials are needed due to small sample sizes in current studies.
Area of Science:
- Neonatal Medicine
- Pediatric Critical Care
- Respiratory Physiology
Background:
- Permissive hypercapnia is known to reduce mortality and ventilation duration in adults.
- Its efficacy and safety in preterm infants receiving mechanical ventilation remain controversial.
Purpose of the Study:
- To evaluate the efficacy and safety of permissive hypercapnia compared to normocapnia in preterm infants requiring mechanical ventilation.
Main Methods:
- A systematic review and meta-analysis of published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies.
- Data extraction and risk of bias assessment were performed independently by two reviewers.
- Meta-analysis of RCTs utilized a random-effects model.
Main Results:
- Four RCTs and one cohort study involving 693 and 371 infants, respectively, were included.
- No significant differences were found between permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) or a composite outcome of death or BPD (very low certainty of evidence).
- Permissive hypercapnia may potentially increase the risk of necrotizing enterocolitis, though this finding is uncertain (very low certainty of evidence).
Conclusions:
- Permissive hypercapnia demonstrated no significant benefits or harms in preterm infants.
- Current studies have sample sizes below optimal levels, highlighting the necessity for additional research to confirm these findings.
Context:
In adults, permissive hypercapnia reduces mortality and ventilation duration. However, in preterm infants, the findings from past research regarding the efficacy and safety of permissive hypercapnia are controversial.
Objective:
To evaluate the efficacy and safety of permissive hypercapnia versus normocapnia in preterm infants on mechanical ventilation.
Data Sources:
MEDLINE, EMBASE, CENTRAL, and CINAHL STUDY SELECTION: Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included.
Data Extraction:
Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated certainty of evidence (CoE) according to the Grading of Recommendations Assessment and Development and Evaluation approach. A meta-analysis of RCTs was performed using the random-effects model.
Results:
Four RCTs (693 infants) and one cohort study (371 infants) were included. No significant differences existed between the permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.74-1.18; very low CoE) and a composite outcome of death or BPD (RR, 1.05; 95% CI, 0.90-1.23; very low CoE). Permissive hypercapnia may increase necrotizing enterocolitis (RR, 1.69; 95% CI, 0.98-2.91; very low CoE), but the null or trivial effect cannot be excluded. No significant differences existed between the two groups for any other outcome assessed (very low-to-low CoE).
Limitations:
The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials.
Conclusions:
Permissive hypercapnia did not have any significant benefit or harm in preterm infants.
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